Conserved Noncoding Elements Follow Power-Law-Like Distributions in Several Genomes as a Result of Genome Dynamics

Abstract

Conserved, ultraconserved and other classes of constrained elements (collectively referred as CNEs here), identified by comparative genomics in a wide variety of genomes, are non-randomly distributed across chromosomes. These elements are defined using various degrees of conservation between organisms and several thresholds of minimal length. We here investigate the chromosomal distribution of CNEs by studying the statistical properties of distances between consecutive CNEs. We find widespread power-law-like distributions, i.e. linearity in double logarithmic scale, in the inter-CNE distances, a feature which is connected with fractality and self-similarity. Given that CNEs are often found to be spatially associated with genes, especially with those that regulate developmental processes, we verify by appropriate gene masking that a power-law-like pattern emerges irrespectively of whether elements found close or inside genes are excluded or not. An evolutionary model is put forward for the understanding of these findings that includes segmental or whole genome duplication events and eliminations (loss) of most of the duplicated CNEs. Simulations reproduce the main features of the observed size distributions. Power-law-like patterns in the genomic distributions of CNEs are in accordance with current knowledge about their evolutionary history in several genomes.

Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization

“…Such a mechanism would protect genome integrity in the body overall and, at the organ-ismal level, promote ultraconservation over evolutionary timescales. Consistent with this model, UCEs are associated with regions of elevated synteny (Dimitrieva and Bucher, 2012; Dong et al, 2009; Irimia et al, 2012; Kikuta et al, 2007; Polychro-nopoulos et al, 2014, 2016; Sandelin et al, 2004; Sun et al, 2006, 2009). Furthermore, and in line with our proposal that disruptions of UCEs or UCE pairing lead to loss of fitness, the genomes of healthy individuals are generally not disrupted in the vicinity of UCEs (Chiang et al, 2008; Derti et al, 2006; McCole et al, 2014), while this pattern does not hold for genomes representing the cancerous state, or individuals with neurodevelopmental disorders or mental delay and congenital anomalies (Martínez et al, 2010; McCole et al, 2014).…”

Ultraconserved elements occupy specific arenas of three-dimensional mammalian genome organization

“…Turning to loop anchors, their lack of enrichment in UCEs chimes with other findings arguing that loops are evolutionarily dynamic (32). Their dynamic nature is consistent with the malleability of enhancers over evolutionary time and thus, also, of enhancer-promoter interactions, both of which make the lack of enrichment for UCEs in loop anchors unsurprising.…”

“…Such a mechanism would protect genome integrity in the body overall and, at the organismal level, promote ultraconservation over evolutionary timescales. Consistent with this model, UCEs are associated with regions of elevated synteny between different species (2,(28)(29)(30)(31)(32)(33)(34)(35).…”

Evolutionary dynamics of hybridization and introgression following the recent colonization of Glossy Ibis (Aves: Plegadis falcinellus) into the New World

“…However, the rapid decay of Moran's I in cline parameters suggests that the variable loci used for cline analyses may not be impacted by processes responsible for conservation in the nearby UCEs. The nonrandom dispersion of UCEs across the genome (Bejerano et al, ; Kim & Pritchard, ; Polychronopoulos, Sellis, & Almirantis, ), on the other hand, may be more problematic. If regions of elevated divergence or reduced introgression tend to occur in areas without UCEs, they may not be represented in our data set.…”